Septic shock is a syndrome produced by the body's response to microorganisms or their toxic products. The incidence of septic shock has been increasing steadily. It carries a mortality of 40 to 90 percent and has become the leading cause of death in intensive care units in the United States. The pathophysiology of the syndrome is remarkably complex; an array of exogenous toxins and endogenous mediators may lead to progressive multi-system organ failure during a period of hours to days, through mechanisms that are still poorly understood. Over the past 12 years, the NIH Septic Shock Protocol (82-CC-123) has produced important insights into the pathophysiology, natural history, and therapy of septic shock. Under the protocol, investigations are continuing, in adult and pediatric patients, of the cardiac and peripheral vascular manifestations of sepsis (using echocardiography and measurement of forearm blood flow), the interplay of exogenous and endogenous mediators of the sepsis syndrome (using blood specimens drawn from septic patients and nonseptic control patients), and the pathogenesis of sepsis-related adult respiratory distress syndrome (using bronchoalveolar lavage).